Toll-like receptor 2 is critical for induction of Reg3 beta expression and intestinal clearance of Yersinia pseudotuberculosis.

Gut. 2009 Jun;58(6):771-6. doi: 10.1136/gut.2008.168443.

Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer’s patches that are Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the Peyer’s patches and succumbed to sepsis independently of nucleotide-binding and oligomerisation domain 2 (NOD2). Recognition of both microbiota-derived and myeloid differentiation factor 88 (MyD88)-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3 beta requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3 beta expression in Peyer’s patches. Importantly, oral treatment with exogenous TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced expression of Reg3 beta and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3 beta resulted in impaired clearance of the bacterial load in Peyer’s patches.

Dessein R, Gironella M, Vignal C, Peyrin-Biroulet L, Sokol H, Secher T, Lacas-Gervais S, Gratadoux JJ, Lafont F, Dagorn JC, Ryffel B, Akira S, Langella P, Nùñez G, Sirard JC, Iovanna J, Simonet M, Chamaillard

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